Aberrant labor is a major clinical problem resulting in significant infant morbidity in spite of recent advances in obstetrical and neonatal care. The mechanisms that control labor onset and its progression, term or preterm, are not well understood. Rupture of the fetal membranes (ROM) is an integral event to the onset and development of the labor process. ROM usually follows the onset of uterine contractions. However, in 10% of term and 40% of preterm births, ROM is the sentinel event leading to uterine contractions and delivery. Thus, the mechanism of ROM has both physiological and clinical importance. Previous thinking that ROM results exclusively from physical stretch forces produced by uterine contractions has evolved to theories that ROM, at term, is a maturational event culminating from a gene controlled program of membrane weakening, including collagen modification and apoptosis. Preterm ROM, initiated in some cases by infection inflammation, and by as yet unknown causes in others, may involve premature activation of the same developmental program. Considerable work has been reported by us and other researchers documenting the ability of various agents to cause apoptosis in cultured cells derived from fetal membranes. However, there has been no direct demonstration that apoptosis and/or remodeling lead to membrane weakening, or to changes in membrane viscoelastic properties which make rupture more likely. We hypothesize that human fetal membranes weaken during gestation as a result of a combination of two processes: programmed biochemical changes leading to collagen remodeling and apoptosis, and superimposed physical stretch forces leading to tissue damage. Further, we suggest that stretch also initiates biochemical changes, which modify membrane viscoelastic properties. We propose a study documenting the one-to-one correspondence of the biochemical changes - apoptosis and membrane remodeling - and the physical weakening of the membranes. Initially we will determine the biochemical/histological characteristics over the topological surface of the fetal membranes and compare them with strength, and other physical properties. Second, we will prospectively inflict precise membrane damage with apoptotic agents or with physical forces and determine the resulting changes in histology and membrane strength. Finally, we will determine the requirements for membrane self repair after physical or biochemically mediated damage. Understanding the relationship between biochemical changes and physical properties of the fetal membranes may allow monitoring of, and/or intervention in, pregnancies at risk for premature delivery due to premature ROM.